Synthetic mammalian pattern formation driven by differential diffusivity of Nodal and Lefty.,Nature Communications

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Synthetic mammalian pattern formation driven by differential diffusivity of Nodal and Lefty.
Nature Communications ( IF 14.7 ) Pub Date : 2018-12-21 , DOI: 10.1038/s41467-018-07847-x
Ryoji Sekine ₁ , Tatsuo Shibata ₂ , Miki Ebisuya _{1,

3}

Affiliation

A synthetic mammalian reaction-diffusion pattern has yet to be created, and Nodal-Lefty signaling has been proposed to meet conditions for pattern formation: Nodal is a short-range activator whereas Lefty is a long-range inhibitor. However, this pattern forming possibility has never been directly tested, and the underlying mechanisms of differential diffusivity of Nodal and Lefty remain unclear. Here, through a combination of synthetic and theoretical approaches, we show that a reconstituted Nodal-Lefty network in mammalian cells spontaneously gives rise to a pattern. Surprisingly, extracellular Nodal is confined underneath the cells, resulting in a narrow distribution compared with Lefty. The short-range distribution requires the finger 1 domain of Nodal, and transplantation of the finger 1 domain into Lefty shortens the distribution of Lefty, successfully preventing pattern formation. These results indicate that the differences in localization and domain structures between Nodal and Lefty, combined with the activator-inhibitor topology, are sufficient for reaction-diffusion patterning.

中文翻译：

由Nodal和Lefty的不同扩散率驱动的合成哺乳动物图案形成。

尚未建立合成的哺乳动物反应扩散模式，并且已经提出了Nodal-Lefty信号转导来满足模式形成的条件：Nodal是一种短程激活剂，而Lefty是一种长程抑制剂。但是，这种图案形成的可能性从未得到直接测试，并且Nodal和Lefty的差异扩散率的潜在机制仍不清楚。在这里，通过综合和理论方法的结合，我们表明在哺乳动物细胞中重构的Nodal-Lefty网络自发地产生了一种模式。出人意料的是，细胞外的结节被限制在细胞的下面，与Lefty相比导致狭窄的分布。短程分布需要Nodal的手指1域，将手指1域移植到Lefty中会缩短Lefty的分布，成功防止图案形成。这些结果表明，节点和Lefty之间的本地化和域结构的差异，结合活化剂-抑制剂拓扑结构，足以用于反应扩散模式。

更新日期：2018-12-21

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